Angiotensin-converting enzyme 2 gene transfer attenuates neointimal formation after carotid artery ischemia-reperfusion injury in rats
10.3760/cma.j.issn.0253-3758.2013.09.011
- VernacularTitle:血管紧张素转换酶2基因转染抑制大鼠颈总动脉缺血再灌注损伤后内膜新生
- Author:
Xu-Wei WU
1
;
Zhou-Qiang LU
;
Jing-Jing GONG
;
Hua-Jun WANG
;
Chang-Sheng XU
;
Xue-Qing JIN
Author Information
1. 福建医科大学附属第一医院心内科福建省高血压研究所
- Keywords:
Peptidyl-dipeptidase A;
Tunica intima;
Neovascularization,pathologic;
Reperfusion injury
- From:
Chinese Journal of Cardiology
2013;41(9):771-777
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effects of lentiviral recombinant angiotensin-converting enzyme 2 (LV-ACE2) gene transfer on the neointimal formation after carotid artery ischemia-reperfusion injury (IRI) and related mechanisms.Methods IRI was induced in SD rats through the carotid artery clipping and rats were divided into IRI,IRI + LV-GFP,IRI + LV-ACE2,IRI + paclitaxel groups (n =10each).Sham operated rats serve as normal control.Four weeks later,neointimal formation was observed on HE stained carotid artery sections.The protein expression of ACE2,α-SM-actin,CD31,AT1R and P-ERK were detected by immunohistochemistry.Results (1) Carotid artery neointimal hyperplasia was readily shown in IRI group [I/M:1.517 ± 0.151 (4 weeks later) vs.0.011 ± 0.004 (Sham),P ＜ 0.01],which was significantly reduced in IRI + LV-ACE2 (0.71 ± 0.17) and IRI + paclitaxel (0.89 ± 0.21) groups.(2) The growth of vascular smooth muscle cells and neovascularization were also significantly inhibited in IRI + LV-ACE2 group and the expression of α-SM-actin (5 843 ± 839 vs.12 648 ± 1 760,P ＜ 0.01) and CD31 [(12.40±4.01)/mm2vs.(96.20±17.79)/mm2,P＜0.01],AT1R (1 219 ±175 vs.4 861±545,P ＜0.01) and P-ERK1/2 phosphorylation (1 040 ±215 vs.2 938 ±286,P ＜0.01) in the neointimal of the injury arteries in IRI + LV-ACE2 group were significantly downregulated compared to IRI group.Conclusion This data suggest that ACE2 gene overexpression is able to attenuate neointimal formation after ischemia-reperfusion injury possibly through downregulating AT1 receptor expression and signal pathway of ERK1/2 phosphorylation.
